Cardiovascular Mortality Risk Prediction Research Articles

1239-P: The Time Point of Blood Pressure Measurement Rather than the Application of U.S. vs. European Blood Pressure Categorizations Is Important for Cardiovascular Risk Prediction in Patients with the Metabolic Syndrome

This observation study (OS) recorded cardiovascular mortality over 21 years in a cohort of 1497 cardiovascular disease patients (median 65 years), of whom 680 had the metabolic syndrome (MetS). We analyzed the predictive value of blood pressure (BP) when measured at baseline of the OS or when measured in a health survey (HS) having enrolled the identical patients fifteen years prior to the OS, applying varying high BP categorizations from the US (ADA/ACC/AHA) and from Europe (EASD/ESC/ESH). Cardiovascular mortality risk increased with increasing BP categories when measured at HS but not when measured at OS (figure), irrespective of whether US or European BP categorizations were used. According to integrated discrimination improvement, the power of BP to predict cardiovascular mortality did not differ significantly between US and European categorizations (p=0.965), however, the power was significantly higher when using BP measurements at HS instead of at OS (p<0.001). This held true both among patients with the MetS (p=0.017) and also in those without the MetS (p<0.001). We conclude that earlier in life BP (HS) readings outperform BP readings done at a more advanced age (OS baseline) in terms of risk prediction for cardiovascular mortality both in MetS patients and in subjects without the MetS. Disclosure A.Leiherer: None. M.Maechler: None. B.Larcher: None. P.Fraunberger: None. G.Nagel: None. E.Zitt: None. H.Drexel: None. H.Concin: None. W.Brozek: None. A.Muendlein: None. H.Ulmer: None. C.H.Saely: None. T.Plattner: None. A.Vonbank: None. A.Mader: None. L.Sprenger: None.

Cardiovascular mortality risk prediction using objectively measured physical activity phenotypes in NHANES 2003–2006

Increased physical activity (PA) has been associated with a decreased risk of cardiovascular disease (CVD) and mortality. However, most previous studies use self-reported PA instead of objectively measured PA assessed by wearable accelerometers. To the best of our knowledge, there have not been studies that quantified the univariate and multivariate ability of objectively measured PA summaries to predict the risk of CVD mortality. We investigate the ability of objectively measured PA summary variables to predict CVD mortality: as individual predictors, as part of the best multivariate model incorporating traditional predictors, and as additions to the best multivariate model using only traditional CVD predictors. Data were collected in the National Health and Nutrition Examination Survey 2003–2006 waves for US participants aged 50–85. The predictive ability was measured using Concordance, sometimes referred to as the C-statistic. Specifically, we calculated 10-fold cross-validated concordance (CVC) in survey-weighted Cox proportional hazard models. The best univariate predictor of CVD mortality was total activity count (outperformed age). In multivariate models, two of the eight predictors identified using the improvement in CVC threshold of 0.001 were PA measures (CVC = 0.844). The best model without physical activity (7 predictors) had CVC of 0.830. The addition of PA measures to the best traditional model was significantly better at predicting CVD mortality (P < 0.001). Accelerometer-derived PA measures have excellent cardiovascular mortality prediction performance. Wearable accelerometers have a potential for assessment of individuals' CVD mortality risks.

Electrocardiographic parameters of left ventricular hypertrophy and prediction of mortality in hemodialysis patients

BackgroundIn hemodialysis patients, left ventricular hypertrophy (LVH) contributes to high cardiovascular mortality. We examined cardiovascular mortality prediction by the recently proposed Peguero-Lo Presti voltage since it identifies more patients with electrocardiographic (ECG) LVH than Cornell or Sokolow-Lyon voltages.MethodsA total of 308 patients on hemodialysis underwent 24 h ECG recordings. LVH parameters were measured before and after dialysis. The primary endpoint of cardiovascular mortality was recorded during a median 3-year follow up. Risk prediction was assessed by Cox regression, both unadjusted and adjusted for the Charlson Comorbidity Index and the Cardiovascular Mortality Risk Score.ResultsThe Peguero-Lo Presti voltage identified with 21% the most patients with positive LVH criteria. All voltages significantly increased during dialysis. Factors such as ultrafiltration rate, Kt/V, body mass index, sex, and phosphate were the most relevant for these changes. During follow-up, 26 cardiovascular deaths occurred. Post-dialysis Peguero-Lo Presti cut-off as well as the Peguero-Lo Presti and Cornell voltages were independently associated with cardiovascular mortality in unadjusted and adjusted analysis. The Sokolow-Lyon voltage was not significantly associated with mortality. An optimal cut-off for the prediction of cardiovascular mortality was estimated at 1.38 mV for the Peguero-Lo Presti.ConclusionsThe post-dialysis Peguero-Lo Presti cut-off as well as the Peguero-Lo Presti and Cornell voltages allowed independent risk prediction of cardiovascular mortality in hemodialysis patients. Measuring the ECG LVH parameters after dialysis might allow a standardized interpretation as dialysis-specific factors influence the voltages.Graphical abstract

Prognostic value of electrocardiographic abnormalities in adults from the Brazilian longitudinal study of adults’ health

ObjectiveCardiovascular diseases (CVDs) are highly preventable non-communicable diseases. ECG is a potential tool for risk stratification with respect to CVD. Our aim was to evaluate ECG’s role in all-cause and...

Walking pace improves all-cause and cardiovascular mortality risk prediction: A UK Biobank prognostic study.

The purpose of this study was to quantify and rank the prognostic relevance of dietary, physical activity and physical function factors in predicting all-cause and cardiovascular mortality in comparison with the established risk factors included in the European Society of Cardiology Systematic COronary Risk Evaluation (SCORE). We examined the predictive discrimination of lifestyle measures using C-index and R2 in sex-stratified analyses adjusted for: model 1, age; model 2, SCORE variables (age, smoking status, systolic blood pressure, total and high-density lipoprotein cholesterol). The sample comprised 298,829 adults (median age, 57 years; 53.5% women) from the UK Biobank free from cancer and cardiovascular disease at baseline. Over a median follow-up of 6.9 years, there were 2174 and 3522 all-cause and 286 and 796 cardiovascular deaths in women and men, respectively. When added to model 1, self-reported walking pace improved C-index in women and men by 0.013 (99% CI: 0.007-0.020) and 0.022 (0.017-0.028) respectively for all-cause mortality; and by 0.023 (0.005-0.042) and 0.034 (0.020-0.048) respectively for cardiovascular mortality. When added to model 2, corresponding values for women and men were: 0.008 (0.003-0.012) and 0.013 (0.009-0.017) for all-cause mortality; and 0.012 (-0.001-0.025) and 0.024 (0.013-0.035) for cardiovascular mortality. Other lifestyle factors did not consistently improve discrimination across models and outcomes. The pattern of results for R2 mirrored those for C-index. A simple self-reported measure of walking pace was the only lifestyle variable found to improve risk prediction for all-cause and cardiovascular mortality when added to established risk factors.

Total and cardiovascular mortality risk according to KDIGO guidelines classification in type 2 diabetic patients

Background and aimsOur aim was to assess the usefulness of KDIGO 2012 risk classification to predict total and cardiovascular mortality in type 2 diabetes mellitus (DM2). Material and methodsProspective cohort study that included DM2 patients. Clinical end-points were total and cardiovascular mortality. The main predictive variable was KDIGO risk classification, which is a combination of urinary albumin excretion and glomerular filtration rate. The predictive value was evaluated by the integrated discrimination improvement (IDI) index. Results453 patients (39.3% males, aged 64.9 [SD 9.3] and with a mean diabetes duration of 10.4 [SD 7.5] years) were included. During a median follow-up of 13 years, mortality rates per 1000patients/year (26.5 vs. 45.1 vs. 79.2 vs. 109.8; p<0.001) and cardiovascular mortality (8.1 vs. 17.4 vs. 24.7 vs. 57.5; p<0.001) were progressively increased in successive KDIGO categories. In the multivariate analysis, there was also a progressive increase of mortality risk (HR[moderate risk]=1.29; HR[high risk]=1.83; HR[very high risk]=2.15; p=0.016) and cardiovascular mortality risk (HR[moderate risk]=1.73; HR[high risk]=2.27; HR[very high risk]=4.22; p=0.007) in the successive categories. KDIGO classification was able to improve the mortality risk prediction (IDI=0.00888; p=0.047) and cardiovascular mortality risk prediction (IDI=0.01813; p=0.035). ConclusionsKDIGO risk classification can effectively stratify total and cardiovascular mortality risk in DM2 patients.

Prognostic Value of a Novel and Established High-Sensitivity Troponin I Assay in Patients Presenting with Suspected Myocardial Infarction.

High-sensitivity troponin has proven to be a promising biomarker for the prediction of future adverse cardiovascular events. We aimed to assess the prognostic value of high-sensitivity troponin I (hs-TnI) on admission in patients with suspected acute myocardial infarction (AMI) analyzed by a novel (Singulex Clarity cTnI) and established hs-TnI assay (ARCHITECT STAT hs-TnI, Abbott). Hs-TnI was measured in a total of 2332 patients from two prospective cohort studies presenting to the emergency department with suspected AMI. The prognostic impact for overall and cardiovascular mortality of both hs-TnI assays was assessed in the total patient cohort as well as in the subgroups of patients with AMI (n = 518) and without AMI (non-AMI) (n = 1814). Patients presenting with highest hs-TnI levels showed higher overall and cardiovascular mortality rates compared to those with lower troponin levels, irrespective of the assay used. Both hs-TnI assays indicated association with overall mortality according to adjusted hazard ratio (HR) among the entire study population (HR for Singulex assay: 1.16 (95% CI 1.08–1.24) and HR for Abbott assay: 1.17 (95% CI 1.09–1.25)). This finding was particularly pronounced in non-AMI patients, whereas no association between hs-TnI and overall mortality was found in AMI patients for either assay. In non-AMI patients, both assays equally improved risk prediction for cardiovascular mortality beyond conventional cardiovascular risk factors. Hs-TnI is independently predictive for adverse outcomes in patients with suspected AMI, especially in the subset of patients without confirmed AMI. There was no difference between the established and the novel assay in the prediction of mortality.

Riesgo de mortalidad total y cardiovascular según la clasificación propuesta por las guías KDIGO en pacientes con diabetes tipo 2

Background and aimsOur aim was to assess the usefulness of KDIGO 2012 risk classification to predict total and cardiovascular mortality in type 2 diabetes mellitus (DM2). Material and methodsProspective cohort study that included DM2 patients. Clinical end-points were total and cardiovascular mortality. The main predictive variable was KDIGO risk classification, which is a combination of urinary albumin excretion and glomerular filtration rate. The predictive value was evaluated by the integrated discrimination improvement (IDI) index. Results453 patients (39.3% males, aged 64.9 [SD 9.3] and with a mean diabetes duration of 10.4 [SD 7.5] years) were included. During a median follow-up of 13 years, mortality rates per 1000 patients/year (26.5 vs. 45.1 vs. 79,2 vs. 109,8; p<0,001) and cardiovascular mortality (8.1 vs. 17.4 vs. 24.7 vs. 57.5; p<0,001) were progressively increased in successive KDIGO categories. In the multivariate analysis, there was also a progressive increase of mortality risk (HR[moderate risk]=1.29; HR[high risk])=1.83; HR[very high risk]=2.15; p=.016) and cardiovascular mortality risk (HR[moderate risk]=1.73; HR[high risk]=2.27; HR[very high risk]=4.22; p=.007) in the successive categories. KDIGO classification was able to improve the mortality risk prediction (IDI=0.00888; p=.047) and cardiovascular mortality risk prediction (IDI=0.01813; p=.035). ConclusionsKDIGO risk classification can effectively stratify total and cardiovascular mortality risk in DM2 patients.

Circulating proteins as predictors of cardiovascular mortality in end-stage renal disease

IntroductionProteomic profiling of end-stage renal disease (ESRD) patients could lead to improved risk prediction and novel insights into cardiovascular disease mechanisms. Plasma levels of 92 cardiovascular disease-associated proteins were assessed by proximity extension assay (Proseek Multiplex CVD-1, Olink Bioscience, Uppsala, Sweden) in a discovery cohort of dialysis patients, the Mapping of Inflammatory Markers in Chronic Kidney disease cohort [MIMICK; n = 183, 55% women, mean age 63 years, 46 cardiovascular deaths during follow-up (mean 43 months)]. Significant results were replicated in the incident and prevalent hemodialysis arm of the Salford Kidney Study [SKS dialysis study, n = 186, 73% women, mean age 62 years, 45 cardiovascular deaths during follow-up (mean 12 months)], and in the CKD5-LD-RTxcohort with assessments of coronary artery calcium (CAC)-score by cardiac computed tomography (n = 89, 37% women, mean age 46 years).ResultsIn age and sex-adjusted Cox regression in MIMICK, 11 plasma proteins were nominally associated with cardiovascular mortality (in order of significance: Kidney injury molecule-1 (KIM-1), Matrix metalloproteinase-7, Tumour necrosis factor receptor 2, Interleukin-6, Matrix metalloproteinase-1, Brain-natriuretic peptide, ST2 protein, Hepatocyte growth factor, TNF-related apoptosis inducing ligand receptor-2, Spondin-1, and Fibroblast growth factor 25). Only plasma KIM-1 was associated with cardiovascular mortality after correction for multiple testing, but also after adjustment for dialysis vintage, cardiovascular risk factors and inflammation (hazard ratio) per standard deviation (SD) increase 1.84, 95% CI 1.26–2.69, p = 0.002. Addition of KIM-1, or nine of the most informative proteins to an established risk-score (modified AROii CVM-score) improved discrimination of cardiovascular mortality risk from C = 0.777 to C = 0.799 and C = 0.823, respectively. In the SKS dialysis study, KIM-1 predicted cardiovascular mortality in age and sex adjusted models (hazard ratio per SD increase 1.45, 95% CI 1.03–2.05, p = 0.034) and higher KIM-1 was associated with higher CACscores in the CKD5-LD-RTx-cohort.ConclusionsOur proteomics approach identified plasma KIM-1 as a risk marker for cardiovascular mortality and coronary artery calcification in three independent ESRD-cohorts. The improved risk prediction for cardiovascular mortality by plasma proteomics merit further studies.

Abstract P148: C-Reactive Protein (CRP) and the Prediction of Cardiovascular Death Among Mexican-Americans

Background: Addition of C-reactive protein (CRP) improves risk stratification provided by traditional Framingham risk factors (FRFs) in some populations, but findings vary by gender and by race/ethnicity. Whether CRP levels can improve risk prediction of cardiovascular mortality (CVD) among elderly Hispanics is unknown. Hypothesis: CRP will add incremental CVD risk prediction in addition to FRFs. Methods: We evaluated whether addition of baseline CRP to the Framingham risk score can improve CVD risk stratification for CVD death among 1,422 participants (536 males, 886 females) from the Sacramento Area Latino Study on Aging (SALSA). SALSA is a well-characterized, NIH funded cohort study of Mexican Americans aged &gt; 60 followed since 1998–1999. Death was ascertained by participant contacts, obituary reviews and cause of death from death certificates. We evaluated the association of CRP levels with CVD death using Cox proportional hazards models adjusting for FRFs stratified by gender. We calculated gender stratified net reclassification improvement (NRI) in models with and without CRP to predict 10-year CVD risks using the established FRFs categories (&lt;5%, 5–10%, 10–20%, &gt; 20%). Results: Mean baseline age was 70.7 and mean CRP level was 5.86 ng/ml. There were 167 CVD male deaths (mortality rate 39.2 per 1,000 person years) and174 among women (mortality rate 27.8 per 1,000 person years). Higher CRP levels were significantly associated with higher CVD mortality risk in men, HR of 1.29 (95% CI 1.11 – 1.50) but not women, HR 0.94 (95% CI 0.81 – 1.08) after adjustment for covariates. Addition of CRP was useful in reclassifying CVD death risk among men defined by FRF alone, and this was due to correct reclassification of those who did not experience CVD death from the highest risk group to a lower risk category. The majority of male participants (619/745=83%) were classified as having &gt;20%risk in the model without CRP. Mortality rate for men initially classified as having &gt; 20% risk was 37.9 per 1,000 person years. After addition of CRP, 6% were reclassified into an intermediate risk category (NRI 7.4%, p&lt; 0.001) and their mortality rate was 10.3 per 1,000 person years. Overall, NRI for men was 4.2% (p=0.05). In contrast, addition of CRP among women was associated with increased misclassification to a higher risk category (NRI= − 13.4%, p=0.0001). Conclusion: A risk prediction model that includes CRP improves cardiovascular risk classification among elderly Mexican-American men but not women as defined by traditional FRFs.